A hemorrhage of a blood vessel, body tissue, organ or bone can result in blood loss leading to hypovolemic shock and death. In hemophiliacs and patients receiving anticoagulant medication, such as often prescribed post-operatively for heart surgery, the problem of rapid blood loss is even more acute.
Attempts have been made to devise a fast, effective and inexpensive method for curbing blood loss, including pastes containing coagulation-enhancing factors. One such coagulation enhancing substance employed to assist a cessation of bleeding or "hemostasis" is human fibrinogen, most commonly employed as a "fibrin glue".
Fibrin glue is composed of a mixture of human fibrinogen and bovine thrombin. It is sold as a kit containing separate vials of fibrinogen and thrombin solutions. These solutions are mixed together and applied to the wound in various ways, including as a paste, as a spray or on a patch.
Fibrin glue, however, is an inconsistent and ineffective therapy for hemostasis. The mixing, soaking, and coating of a patch with fibrin glue requires time-consuming and cumbersome procedures. Each of the preparation steps introduces potential errors and thus their efficacy varies with the experience of operating room personnel. Moreover, during the preparation of such solution, further hemorrhage occurs and the solutions are washed away by intense bleeding. Despite the headway made in fibrinogen compositions and surgical techniques, these pitfalls in achieving hemostasis underscore the need for development of a suitable product.
An improvement over fibrin glue, marketed in Europe consists of a biodegradable collagen patch onto which is impregnated bovine thrombin, aprotinin and human fibrinogen (the "TAF" patch). An example of a TAF patch is the TachoComb.RTM. patch marketed in Europe by Hafslund Nycomed Pharma, DE. The patch also contains calcium chloride to enhance coagulation. In use, this patch is removed from its package, dipped into saline solution and applied to the bleeding organ with light pressure for at least five minutes. When the bleeding has stopped, the patch is left in place by the surgeon and the cavity closed.
A major drawback to the use of fibrin glue and the TAF patch is that both contain human fibrinogen, a protein purified from human blood. Because of the high risk of HIV and hepatitis viral contamination, the Food and Drug Administration revoked the use of human fibrinogen in the United States in 1978. In addition to the safety concerns, human fibrinogen purified from human plasma is very expensive.
A TAF patch also requires refrigeration in order to stabilize the coagulation-enhancing agents contained in the patch. This requirement prohibits certain field applications of the patch, where refrigeration facilities are unavailable. Another problem with a TAF patch that surgeons cite is its inflexibility, that is, the patch does not conform easily to the shape of the body surface to which it is applied.
A hemorrhage of a parenchymal organ, such as the spleen, liver, lung or pancreas, which can result from trauma or surgery, is particularly difficult to treat. Parenchymal organs are difficult to ligate because the tissue is easily torn, pulverized or crumbled. As a result, surgeons often resort to the use of electrocautery, which can lead to further destruction of the patient's tissues.
Thus, an effective hemostatic patch is desired which is safe from deadly viral contamination and even stops bleeding in the problematic hemorrhages of parenchymal organs. A patch is further desired that is inexpensive, easy to use and that molds easily to body contours. Also a need exists for a patch that withstands elevated temperatures without requiring refrigeration and retains hemostatic efficacy.